Pharmacokinetics and clinical effect during continuous epidural infusion with ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief

Background: Ropivacaine has shown less systemic toxicity than bupivacaine, and comparatively low muscle-blocking properties could constitute another advantage when used epidurally for obstetric pain relief. We aimed primarily to compare maternal and foetal drug disposition following continuous epidural infusion of ropivacaine or bupivacaine.
Methods: Twenty-four full-term, nulliparous women were randomized to continuous epidural infusion (10 ml/h) of ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief in a double-blind, parallel-group design. Maternal blood samples were collected up to 24 h after the end of infusion as well as taken from the umbilical cord at the time of delivery. Sensory and motor block as well as analgesia were assessed. All the women were monitored by cardiotocography and neonatal assessment was performed.
Results: The sensory block was adequate for both drugs. Higher plasma levels (total and free) were seen with ropivacaine, although the infusion with bupivacaine continued on average for about 2 hours longer. However, the ratios between maternal and umbilical blood concentrations were similar for both drugs. Normal neonatal Apgar and neonatal adaptive capacity scores (NACS) were found in both groups.
Conclusion: A continuous epidural infusion of 25 mg/h ropivacaine or bupivacaine both produced good labour pain relief. Higher total and free plasma concentrations were seen for ropivacaine. The ratios between maternal and umbilical plasma levels were similar for both drugs.     

Continuous infusion epidural analgesia for obstetrics: bupivacaine versus bupivacaine-fentanyl mixture

Continuous infusion epidural analgesia (CIEA) using a mixture of bupivacaine and fentanyl was evaluated in this randomized, double-blind study involving 75 nulliparous women by comparing the mixture (Group I, Bupivacaine 0.125% and fentanyl 4 micrograms.ml-1 -24 patients) with two concentrations of bupivacaine alone (Group II, bupivacaine 0.25% - 24 patients; and Group III, bupivacaine 0.125% - 27 patients). Epidural anaesthesia was established in Group I with 6 ml 0.125% bupivacaine with fentanyl 50 micrograms and in both Groups II and III with 6 ml 0.25% bupivacaine. In the women whose pain score (Visual Analogue Scale) decreased by at least 50% within 15 min, CIEA was given until delivery. The initial infusion rate in all three groups was set at 7 ml.hr-1, but was decreased in the event of motor block or excessive sensory level. For inadequate analgesia, bupivacaine 0.25% in 3 ml supplements was given every 30 min, as required. During the first stage of labour, 88% of women in Group I reported excellent or good analgesia compared with 92% of women in Group II (NS) and with 59% in Group III (P less than 0.05). The proportion of women reporting excellent/good analgesia during the second stage was approximately 65% in all three groups. The total cumulative dose of bupivacaine in Group I was 54 +/- 36 mg, compared with 107 +/- 47 mg for Group II (P = 0.001), and 71 +/- 41 mg for Group III (NS). Group I patients required less supplementation with bupivacaine than either Group II or III patients during the first stage but only with Group III patients during the second stage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of continuous epidural bupivacaine infusion plus either continuous epidural infusion or patient-controlled epidural injection of fentanyl for postoperative analgesia.

We compared the postoperative epidural analgesia provided by the continuous epidural infusion of bupivacaine supplemented with patient-controlled injection (PCA) of epidural fentanyl with that provided by a continuous infusion of bupivacaine supplemented with a continuous epidural infusion of fentanyl. Our patient population comprised 16 ASA physical status I or II patients undergoing laparotomy with a midline incision under general anesthesia combined with bupivacaine epidural analgesia. Post-operatively, a continuous epidural infusion of bupivacaine (0.1 mg.kg-1.h-1) was combined with epidural fentanyl given by either (a) PCA (15-micrograms bolus with a lockout interval of 12 min, n = 8) or (b) continuous infusion (1 microgram.kg-1.h-1, n = 8). In the case of inadequate pain relief in the latter group, the fentanyl infusion rate was increased by 10 micrograms/h. Analgesia evaluated by a visual analogue pain score and by a verbal pain score was similarly effective in both groups. The sedation score was also similar in both groups. The total dose of epidural fentanyl administered during the first 24 h was significantly lower in the PCA group than in the continuous infusion group (405 +/- 110 micrograms vs 1600 +/- 245 micrograms, P less than 0.001). The dose of fentanyl given during each 4-h interval ranged between 40 and 160 micrograms in the PCA group and 251 and 292 micrograms in the continuous infusion group. Clinically detectable respiratory depression was not observed in either group. In conclusion, epidural administration of 0.1 mg.kg-1.h-1 bupivacaine combined with fentanyl provides effective postoperative analgesia with a total dose of fentanyl required that is lower when fentanyl is administered by epidural PCA rather than by continuous epidural infusion.     

Postoperative analgesia using continuous lumbar epidural infusion of ropivacaine in comparison with bupivacaine

BACKGROUND: Epidural bupivacaine infusion is a commonly used technique for postoperative analgesia because of its motor-sparing properties. Recently a new long acting local anesthetic, ropivacaine, has become available. The aim of this study was to investigate the efficacy of ropivacaine and bupivacaine with regard to postoperative analgesia when administered continuously into the lumbar epidural space. METHODS: All patients were ASA I II and undergoing ipsi-lateral leg orthopedic surgery with epidural or combined spinal-epidural anesthesia. Patients were randomly assigned to following three groups: 0.1% ropivacaine (0.1 R); 0.2% ropivacaine (0.2 R); 0.125% bupivacaine (0.125 B). At the end of surgery, continuous infusion was begun at a rate of 6 ml.hr 1 after a bolus epidural administration of 5 ml of 0.2% ropivacaine in R groups and 0.25% bupivacaine in B group. Sensory and motor block, blood pressure, pulse rate, verbal pain score (VPS), analgesic consumption were assessed at 20 min, 1, 3, 10-20 hrs following the beginning of continuous infusion. RESULTS: Vital signs were stable at every measuring point in all groups. In 0.1 R group (n = 20), the spread of sensory block at 3 hrs after infusion was lower than 0.2 R group (n = 19), and VPS during the study was higher than 0.125 B group (n = 17). Bromage scale after 3 hrs was higher in 0.2 R group compared with 0.125 B group. The degree of sensory and motor block gradually decreased, resulting in little difference between the groups. When epidural anesthesia was spread over the surgical area throughout the study, 0.2 R or 0.125 B was sufficiently relieved from postoperative pain. CONCLUSIONS: After leg orthopedic surgery, 6 ml.hr-1 of 0.2 R or 0.125 B provided enough postoperative analgesia when the spread of anesthesia covered the operated area. 0.2 R would be better compared to 0.125 B in continuous epidural infusion for postoperative analgesia due to less systemic toxicity, even though it accompanies a little more intense motor block.     

Plasma concentrations of bupivacaine in young infants after continuous epidural infusion

This study reports plasma bupivacaine concentration in seven infants who during major abdominal surgery received lumbar epidural or caudal block anaesthesia. Plasma concentrations (CP) were measured postoperatively after six and twelve h of continuous infusion. Postnatal age ranged from one day to seven months. The local anaesthetic block was performed after induction of anaesthesia. Postoperatively bupivacaine 1.25-2.5 mg·ml^?1 without adrenaline was infused at a rate of 0.5 to 0.83 mg·kg^?1·h^?1. After six h of infusion the mean value measured was 1.59 μg·ml^?1 (range 1.2-1.94 μg·ml^?1). After 12 h the mean value measured was 2.06 μg·ml^?1 (range 1.53-2.98 μg·ml^?1). A marked increase in bupivacaine plasma concentration was seen between six and 12 hours of infusion. Bupivacaine plasma concentration never exceeded 4 μg·ml^?1. Adverse effects that possibly were due to a toxic reaction to bupivacaine were seen in three patients. In conclusion, the dose administered in this study appears to be high and cannot be recommended as safe dosage in this age group.;     

Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with and without biliary atresia

BACKGROUND: Continuous epidural infusion of bupivacaine is widely practiced for postoperative pain relief in pediatric patients. However, bupivacaine may induce adverse effects in infants (convulsions or cardiac arrhythmias), likely because of decreased hepatic clearance and serum protein binding capacity. The authors wanted to examine the complex relations between age, alpha-1 acid glycoprotein (AAG) concentration, and unbound and total bupivacaine serum concentrations in infants receiving bupivacaine epidurally for 2 days. METHODS: Twenty-two infants aged 1-7 months (12 with biliary atresia and 10 with another disease) received a continuous epidural infusion of 0.375 mg x kg(-1) x h(-1) bupivacaine during 2 days (during and after surgery). Unbound and total bupivacaine concentration in serum was measured 0.5, 4, 24, and 48 h after infusion initiation. AAG concentration was measured in serum before and 2 days after surgery. In eight additional infants, the blood/plasma concentration ratio was measured in vitro at whole blood concentrations of 2 and 20 microg/ml. Bupivacaine concentration was fitted to a one-compartment model to calculate basic pharmacokinetic parameters. RESULTS: No adverse effects were observed. AAG increased markedly after surgery, and the increase was correlated to both age and preoperative AAG concentration. Two infants aged 1.8 months had unbound concentrations greater than 0.2 microg/ml. Clearance of unbound drug significantly increased with age. Because of increased drug binding, clearance of bound drug decreased both with time (from 0.5 to 48 h) and with age. Blood/plasma ratio was 0.77+/-0.08 and 0.85+/-0.24 at 2 and 20 microg/ml, respectively. CONCLUSIONS: Because of a low AAG concentration and a low intrinsic clearance, unbound bupivacaine increased to concentrations greater than 0.2 microg/ml in two infants younger than 2 months, after 2 days of infusion at a rate of 0.375 mg x kg(-1) x h(-1). The increase in AAG observed after surgery did not fully buffer this unbound fraction. Similarly, the buffer capacity of erythrocytes did not sufficiently increase at high concentration to compensate the saturation of the AAG system. Thus, we propose the use of a maximum dose of 0.25 mg x kg(-1) x h(-1) in infants younger than 4 months and a maximum of 0.3 mg x kg(-1) x h(-1) in infants older than 4 months.     

Comparison of continuous epidural infusion of morphine/bupivacaine with fentanyl/ bupivacaine for postoperative pain relief

The efficacy and safety of postoperative analgesia with continuous epidural infusion of either morphine or fentanyl in combination with bupivacaine were evaluated in 85 patients, ASA physical status I or II, undergoing thoracic and/or upper abdominal surgery. Patients were treated with one of the combinations for 48 h after surgery. The morphine/bupivacaine group (MB; n = 45) received morphine at the rate of 0.2 mg h^-1, and bupivacaine at the rate of 10 mg h^-1 for the first 24 h or 5 mg h^-1 for the second 24 h; the fentanyl/bupivacaine group (FB; n = 40) received fentanyl at the rate of 20 μg–h^-1, and bupivacaine at the rate of 10 mg h^-1 for the first 24 h or 5 mg h^-1 for the second 24 h. The degree of pain relief assessed by the visual pain scale and the modified Prince Henry pain scale was satisfactory in most patients in both groups. In group MB 74% and in group FB 76% of patients did not need any supplementary analgesics. No significant differences were observed between the groups in assessment of pain. The incidence of hypotension ( P < 0.05) and pruritus ( P < 0.05) was higher in group MB than in group FB. None of the patients developed respiratory depression in either group.     

A Simple safe method for continuous infusion epidural analgesia in obstetrics

Continuous infusion epidural anaesthesia may reduce the risks of hypotension, high spinal block and intravenous injection associated with repeated bolus injections. However, controlling the rate of a simple infusion is difficult and infusion pumps are expensive and bulky. We describe a method for continuous infusion epidural anesthesia using a 6ml/hr capillary infusion device (Intraflo CFS-06F Sorenson Research Co., Salt Lake City, Utah) and bupivicaine 0.25 percent. In a study of 50 patients, 35 (70 percent) had adequate pain relief with the infusion alone fora mean time until delivery of 5 hours (range 2 to 13 hours). A further 11 patients (22 per cent) required only one top-up for the second stage of labour after a mean pain-free time of 5.4 hours (range 1.5 to 9.7 hours). There were no maternal or foetal complications related to the technique of continuous infusion used. No block went higher than the ninth thoracic dermatome at any time.     

Clinical experience with atracurium--a continuous infusion technic

A continuous infusion technique for atracurium was investigated. It provided a stable neuromuscular block, with a mean infusion rate of 0.008 mg/kg/min after an initial bolus of 0.5 mg/kg. A wide individual response was found and an arbitrary infusion rate based on mass alone is therefore not possible. The above rate is thus a starting point and should be adjusted according to individual requirements, preferably by using a peripheral nerve stimulator. The technique obviates the need for repeated increments of atracurium during lengthy surgical procedures.     

Postoperative pain relief by continuous epidural infusion of bupivacaine and buprenorphine]

Continuous postoperative pain relief produced by epidural block with bupivacaine and buprenorphine was evaluated in 12 patients after thoracotomy, 19 patients after upper abdominal surgery, and 14 patients after lower abdominal surgery. Patients initially received 8 ml of 0.25% bupivacaine and 0.1 mg of buprenorphine at recovery room in operating theater and continuously received the mixture of 0.25% bupivacaine and 5 micrograms.ml-1 buprenorphine at a rate of 1 ml.h-1 using a portable pump. About fifty percent of the patients did not need additional narcotics during 48 postoperative hours. About ninety percent of the patients needed one additional narcotics during 48 postoperative hours. The authors conclude that epidural analgesia with the mixture of bupivacaine and buprenorphine produces satisfactory postoperative pain relief.     

Continuous infusion epidural analgesia in obstetrics

The effects of 0.08% (Group A) and 0.25% (Group B) solutions of bupivacaine were compared in a random manner, to assess continuous pump infusion epidural analgesia in labour. Both solutions were infused at a dose rate of 20 mg bupivacaine/hour. The results in all the mothers who had received infusions lasting more than 4 hours were studied. There were 25 in Group A and 28 in Group B. Any treatment during the infusion epidural for inadequate analgesia, hypotension, etc., was recorded as an intervention. The mean of the intervention-free intervals was significantly greater in Group A than in Group B, and significantly fewer top-up injections were required in Group A. The results show that the administration of a 0.08% solution of bupivacaine into the epidural space by continuous pump infusion is more labour saving than the infusion of a 0.25% solution. The concept that a greater volume infusion rate maintains a more extended liquid sleeve of local anaesthetic in the epidural space is supported.     

Continuous epidural infusion of bupivacaine in labour

Thirty patients were given a constant epidural infusion in labour by gravity feed drip of approximately 10 ml of 0.25% bupivacaine per hr. The infusion proved a simple and reliable method of ensuring adequate analgesia throughout labour. There were no problems of drug toxicity and the incidence of complications and side effects was comparable to a previous series using intermittent 0.5% bupivacaine.     

Comparison of continuous epidural infusion of fentanyl and bupivacaine with intermittent epidural administration of morphine for postoperative pain management in children

Background: The aim of this study was to compare epidural infusion of bupivacaine and fentanyl and intermittent epidural morphine with regard to analgesic effect, and incidence and severity of side effects in children undergoing major abdominal or genito-urological surgery in order to improve the postoperative pain management of children. Methods: A double-blind, block-randomised study design was used. Thirty-one children aged 3 months to 6 years undergoing major abdominal or genito-urological surgery were studied. After induction of anaesthesia a lumbar epidural catheter was placed at L_3–4 or L_4–5. Postoperatively, the children received either 30 μg/kg of morphine every 8 h or a continuous infusion of fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml at a rate of 0.25 ml.kg^-1.h^-1. All children additionally received rectal paracetamol in doses of 50–100 mg.kg^-1. d^-1 on a regular basis, and if necessary supplementary intravenous morphine in doses of 50 μg/kg. Postoperatively, pain, administration of supplemental morphine and side effects were recorded 5 times by one observer during the day of surgery and the first postoperative day. All children had an epidural catheter throughout the study period. Results: Both regimens provided effective analgesia, but significantly better pain relief was obtained in children receiving the fentanyl/bupivacaine regimen. Sedation, pruritus, vomiting, and administration of antiemetics were seen in both treatment groups, and even though both the incidence and severity of side effects tended to be higher in children receiving morphine, no statistically significant difference was found. No episodes of respiratory depression or motor blockade were noticed. Conclusion: Continuous epidural infusion of fentanyl and bupivacaine was found to be superior to intermittent epidural morphine. The initial regimen should be fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml infused at a rate of 0.25 ml. kg^-1. h^-1.